Suppression of colon cancer metastasis by Aes through inhibition of Notch signaling (Cancer Cell, 2011, 19:125-137)

報告日期: 2011/04/15
報告時間: 17:10/18:00
報告學生: 李永國
講評老師: 張 玲

Full Text:

Suppression of Colon Cancer Metastasis by Aes through Inhibition of Notch Signaling
Cancer Cell. 19, 125–137, January 18, 2011
Masahiro Sonoshita,Masahiro Aoki and and Makoto Mark Taketo
Speaker: Yung-Kuo Li
Commentator: Chang, Christina Ling, Ph.D
Location: Room 602  
Date: 2011/04/15 17:10-18:00
The mechanisms of cancer metastasis consist of local invasion, intravasation, transport, extravasation, formation of micrometastases, and colonization.Owing to patients with metastatic tumor always exhibit poor prognosis and lower survival rate in most malignances, metastasis have become an important target for the development of cancer therapy. Hence, the prevention or reduction of metastatic diseases has attracted many attentions. Here, the authors reported a gene Amino-terminal enhancer of split (Aes), also called Grg5 in mice, was a metastasis suppressor candidate for colon cancer. By using immunohistochemistry staining, they found that both human and mouse colon primary tumors lost AES/Aes at the invasion fronts. Knockdown of Aes promoted the metastasis of Colon26 cells or HCA7 (human colon cancer cells) to liver and lungs. Aes together with TLE1 hold the Rbpj/NICD/Maml1 complex inthe nucleus that inhibited Notch signaling. In colon cancer cells, Notch signaling was introduced by Jagged1/Delta-like 4 (Dll4) on blood vessels and macrophages, and stimulated transendothelial migration (TEM). The Aes knockout micein tissue-specific condition (Apc+/△716 -Aes△ex2/△ex2-TgvCreERT2) (Apc/Aes) also caused tumor invasion and intravasation by activated Notch signaling pathway. Taken together, these results indicated that inhibition of Notch signaling by Aes expression prevents metastasis of colon cancer.
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